Fifteen adults with mastocytosis were entered into a double-blind clinical protocol comparing azelastine, an H1 antihistamine, with mast cell stabilizing properties, with chlorpheniramine. Agents were compared with symptom scores, by analyzing plasma and urine histamine levels, and by comparing suppression of skin test responses to degranulating agents. Initial data analysis suggests that azelastine was superior to chlorpheniramine at suppressing skin test responses and in reducing symptom scores of skin irritability. Azelastine, however, did not lower plasma or urine histamine levels or significantly affect other parameters of disease. Lesional and non-lesional skin of subjects with mastocytosis was analyzed for the distribution and concentration of tryptase positive, chymase negative mast cells (MCr) and tryptase positive, chymase positive mast cells (MCrc) and compared to normal skin and non-lesional skin of subjects with unexplained anaphylaxis or flushing episodes. MCrc cells were the only type of mast cells seen in all specimens analyzed. The concentration of mast cells in the superficial dermis of mastocytosis lesions (40985(+- )217772 mast cells/mm3) was significantly increased over that in corresponding areas of non-lesional skin from subjects with mastocytosis (7178(+-)3607 mast cells/mm3), skin from subjects with idiopathic anaphylaxis of flushing episodes (6974 (+-)3873 mast cells/mm3) and normal skin (7347(+-)2973 mast cells/mm3). The exclusive presence of MCrc cells in skin lesions of mastocytosis which are characterized by non-malignant hyperplasia of mast cells suggests involvement of local tissue factors in mast cell recruitment and differentiation.